Antiseizure medication effects on sleep architecture in epilepsy: Glymphatic insights and implications for cognitive decline

Disruptions in sleep architecture may contribute to cognitive decline in people with epilepsy (PWE), potentially through impaired glymphatic clearance. In this narrative review, we explore how antiseizure medications (ASMs) influence key sleep stages, particularly slow-wave sleep (SWS) and rapid eye movement (REM) sleep, and consider how these changes may intersect with glymphatic function and cognitive outcomes. SWS supports glymphatic clearance of interstitial waste, including neurotoxic solutes such as amyloid-β and tau. Some ASMs appear to enhance SWS, while others suppress it, suggesting the possibility of differential long-term cognitive effects. We propose that sleep disruption may represent an important but underappreciated factor linking epilepsy and neurocognitive decline. While sleep impairment in epilepsy is often attributed to seizures or interictal activity, ASM-induced alterations in sleep architecture may also play a role. However, this relationship remains largely theoretical and requires further experimental study. We also review the use of diffusion tensor image analysis along the perivascular space (DTI-ALPS) as an emerging imaging method to approximate glymphatic activity. Although DTI-ALPS provides a non-invasive proxy for perivascular water diffusivity, it does not directly measure glymphatic clearance and may be affected by factors such as partial volume effects. Its role in epilepsy research remains exploratory and should be interpreted cautiously. To date, no study has directly examined the combined effects of ASMs, sleep structure, and glymphatic function in a single cohort. We outline opportunities for future research integrating neuroimaging, sleep assessment, and cognitive testing to better understand how sleep-targeted strategies might preserve brain health in epilepsy.